In mammalian pregnancy increased sensitivity to a fast is characterized by exaggerated ketosis, hypoglycemia and hypoinsulinemia. The present study assesses the role of deficient gluconeogenic substrate in this process by investigating: a) release of alanine and other substrates from perfused skeletal muscle in vitro from pregnant and control rats; b) the production of glucose and ketone bodies in perfused liver from similar groups of animals. The role of placental steroids, estrogens and progesterone, in the induction of these events is defined by measuring similar parameters in sex steroid-treated animals during starvation and applying this line of investigation to the effects of sex steroids on the sensitivity to fasting in adult women. In related projects the influence of insulin antagonism (induced by pregnancy) and diabetes (streptozotocin method) on insulin and glucagon secretion in perfused rat pancreatic islets in response to various substrates is investigated. Disturbances of bihormonal secretion are related to perturbations in alpha and beta cell content of trace elements by utilizing analytical techniques of scanning electron microscopy and energy-dispersive x-ray analysis.